In patients with neuromuscular diseases, including spinal cord injury (SCI), stroke, and amyotrophic lateral sclerosis (ALS), expiratory muscle weakness and inability to generate an effective cough and clear secretions are a major cause of respiratory complications including bronchitis and pneumonia. In fact, pneumonia is a common cause of death in these patient populations. In a recent human clinical trial, we demonstrated that lower thoracic spinal cord stimulation (SCS) results in activation of the expiratory muscles and the generation of large positive airway pressures and high peak airflow rates characteristic of a normal cough. Restoration of an effective cough resulted in greater ease in raising secretions, reductions in the incidence of respiratory tract infections, and improvement in life quality. Unfortunately, activatin of the respiratory muscles via SCS requires high stimulus amplitudes (40mA), which may also cause unwanted side effects including stimulation of pain fibers and, therefore, this method cannot be applied in patient populations who have intact sensation. We have recently demonstrated in preliminary animal testing that expiratory muscle activation can also be achieved with high frequency (e 300Hz) spinal cord stimulation (HF-SCS) requiring very low stimulus amplitudes (< 2mA). This is a novel and more physiologic method of expiratory muscle activation since stimulation occurs at a pre- motoneuron level, allowing for processing of the stimulus within the motoneuron pools, resulting in a more physiologic recruitment pattern. It is our Hypothesis that HF-SCS will result in sufficient activation of the expiratory muscles to provide large positive airway pressures and high peak expiratory airflow rates necessary to generate an effective cough. Prior to clinical trials, however, there are important aspects of this technique that require further characterization in an animal model. The Specific Objectives of this proposal are to: I) determine the optimal stimulus paradigm and electrode location that result in optimal activation of the expiratory muscles with the consequent development of large positive airway pressures and high peak expiratory airflow rates characteristic of an effective cough, II) evaluate the mechanism by which the expiratory muscles are activated during HF-SCS, and III) evaluate the electric field distribution during HF-SCS with the goal of evaluating alternative electrode designs. The results of these animal studies should resolve important basic science issues concerning this technique and provide the framework for human clinical trials. Restoration of an effective cough may allow patients with various neuromuscular disorders to clear secretions more easily and reduce the morbidity and mortality associated with respiratory complications in these patient populations.